Nonlinear dependence of hydraulic conductivity on tissue deformation during intratumoral infusion

Efficiency of intratumoral infusion for drug and gene delivery depends on intrinsic tissue structures as well as infusion-induced changes in these structures. To this end, we investigated effects of infusion pressure (P-inf) and infusion-induced tissue deformation on infusion rate (Q) in three mouse tumor models (B16.F10, 4T1, and U87) and developed a poroelastic model for interpreting data and understanding mechanisms of fluid transport in tumors. The collagen concentrations in these tumors were 2.9 +/- 1.2, 12.2 +/- 0.9, and 18.1 +/- 3.5 mu g/mg wet wt. of tissues, respectively. During the infusion, there existed a threshold infusion pressure (P-t), below which fluid flow could not be initiated. The values of P-t for these tumors were 7.36, 36.8, and 29.4 mmHg, respectively. Q was a bell-shaped function of P-inf in 4T1 tumors but increased monotonically with increasing P-inf in other tumors. These observations were consistent with results from numerical simulations based on the poroelastic model, suggesting that both the existence of P-t and the nonlinear relationships between Q and P-inf could be explained by infusion-induced tissue deformation that anisotropically affected the hydraulic conductivity of tissues. These results may be useful for further investigations of intratumoral infusion of drugs and genes.